The invention refers to a process for producing 17β-(substituted)-3-oxo-Δ1,2-4-azasteroids by dehydrogenation of 4-azasteroids at position 1,2, as well as to intermediates formed and/or used in said process. Some of said compounds are testosterone-5α-reductase inhibitors and can be used in the treatment of hyperandrogenic disorders.
The synthesis of 17β-(substituted)-3-oxo-Δ1,2-4-azasteroids can be carried out by means of the dehydrogenation of azasteroids, particularly 17β-(substituted)-3-oxo-4-azasteroids, in order to obtain the corresponding compound with a double bond at position 1,2.
The state of the art discloses several processes for dehydrogenating 4-azasteroids and, particularly, 3-oxo-4-azasteroids substituted at position 17β. Spanish patent ES 8,702,430 discloses a process for introducing a double bond at position 1,2 of 4-azasteroids by treatment with benzeneseleninic anhydride in refluxing chlorobenzene. European patent EP 298,652 discloses a dehydrogenation process comprising the oxidation of a silyl enol ether derivative with a DDQ-type quinone [4,5-dichloro-3,6-dioxo-1,4-cyclohexadiene-1,2-dicarbonitrile]. European patents EP 473,225 and 473,226 disclose processes comprising the formation of silyl enol ethers with halides or trialkyisilyl triflates, subsequent addition of halogen to the double bond at position 2,3 and dehydrohalogenation.
European patent EP 428,366 discloses the process shown in the following diagram:

As can be seen, a 17β-(substituted)-3-oxo-4-azasteroid reacts with an oxalyl chloride to form the corresponding adduct which, by means of reaction with bromine, provides the compound 2,3-dibromate. The dibromate intermediate is decomposed into the 2-bromine derivative providing 17β-(substituted)-2-bromo-3-oxo-4-azasteroid by means of reaction with ethylenediamine or 2-methylaminoethanol by means of a transamidation and/or transesterification reaction. The dehydrobromation carried out with conventional reagents gives rise to the dehydrogenation product.
Said European patent EP 428,366 mentions that all intermediates leading to 2-bromo-5α-azasteroid-type products are water sensitive, this one should therefore be strictly excluded from the reaction. According to said European patent, the products of degradation with water of said intermediates are those shown in the following diagram:

Even though such degradation products, both the 3-hydroxy derivative and the 2-bromo-3-hydroxy derivative, are represented in the diagram shown in European patent EP 428,366, said patent discloses neither its obtainment nor its characterization. Likewise, the only example (Example 1) contained in said EP 428,366 discloses a process in which none of the synthesis intermediates are isolated, nor does it provide physical constants or structural identification spectroscopic data.
The majority of processes known for the dehydrogenation of 17β-(substituted)-3-oxo-4-azasteroids comprise the use of toxic selene reagents or reagents which are hazardous to handle (bromine), or expensive, such as trimethylsilyl triflate, therefore there is a need to develop alternative processes which overcome such drawbacks.
The invention proposes a new method for obtaining 17β-(substituted)-3-oxo-Δ1,2-4-azasteroids of formula (I) from 2-(substituted)-3-hydroxyoxazolidinedione of formula (IV).
The solution provided by this invention is based on the fact that the inventors have surprisingly seen that it is possible to carry out the cleavage of the oxazolidinedione ring present in a 2-(substituted)-3-hydroxyoxazolidinedione of formula (IV), using the reaction conditions provided in the invention, to produce a 2-(substituted)-3-oxo-4-azasteroid of formula (V) which, by removal of the substituent group at position 2, provides a 17β-(substituted)-3-oxo-Δ1,2-4-azasteroid of general formula (I) with good yields.
A process like the one provided by this invention has the advantage of not using toxic or hazardous reagents, and furthermore, the intermediates used and/or formed in said process are stable enough in contact with water that they can be easily isolated, purified and stored.